Using Bayesian hierarchical modeling for performance evaluation of clinical trial accrual for a cancer center.

Introduction: Slow patient accrual in cancer clinical trials is always a concern. In 2021, the University of Kansas Comprehensive Cancer Center (KUCC), an NCI-designated comprehensive cancer center, implemented the Curated Cancer Clinical Outcomes Database (C3OD) to perform trial feasibility analyses using real-time electronic medical record data. In this study, we proposed a Bayesian hierarchical model to evaluate annual cancer clinical trial accrual performance. Methods: The Bayesian hierarchical model uses Poisson models to describe the accrual performance of individual cancer clinical trials and a hierarchical component to describe the variation in performance across studies. Additionally, this model evaluates the impacts of the C3OD and the COVID-19 pandemic using posterior probabilities across evaluation years. The performance metric is the ratio of the observed accrual rate to the target accrual rate. Results: Posterior medians of the annual accrual performance at the KUCC from 2018 to 2023 are 0.233, 0.246, 0.197, 0.150, 0.254, and 0.340. The COVID-19 pandemic partly explains the drop in performance in 2020 and 2021. The posterior probability that annual accrual performance is better with C3OD in 2023 than pre-pandemic (2019) is 0.935. Conclusions: This study comprehensively evaluates the annual performance of clinical trial accrual at the KUCC, revealing a negative impact of COVID-19 and an ongoing positive impact of C3OD implementation. Two sensitivity analyses further validate the robustness of our model. Evaluating annual accrual performance across clinical trials is essential for a cancer center. The performance evaluation tools described in this paper are highly recommended for monitoring clinical trial accrual.

Evaluation of the Durability of the Immune Humoral Response to COVID-19 Vaccines in Patients With Cancer Undergoing Treatment or Who Received a Stem Cell Transplant.

Importance: The durability of the antibody response to COVID-19 vaccines in patients with cancer undergoing treatment or who received a stem cell transplant is unknown and may be associated with infection outcomes. Objective: To evaluate anti-SARS-CoV-2 spike protein receptor binding domain (anti-RBD) and neutralizing antibody (nAb) responses to COVID-19 vaccines longitudinally over 6 months in patients with cancer undergoing treatment or who received a stem cell transplant (SCT). Design, Setting, and Participants: In this prospective, observational, longitudinal cross-sectional study of 453 patients with cancer undergoing treatment or who received an SCT at the University of Kansas Cancer Center in Kansas City, blood samples were obtained before 433 patients received a messenger RNA (mRNA) vaccine (BNT162b2 or mRNA-1273), after the first dose of the mRNA vaccine, and 1 month, 3 months, and 6 months after the second dose. Blood samples were also obtained 2, 4, and 7 months after 17 patients received the JNJ-78436735 vaccine. For patients receiving a third dose of an mRNA vaccine, blood samples were obtained 30 days after the third dose. Interventions: Blood samples and BNT162b2, mRNA-1273, or JNJ-78436735 vaccines. Main Outcomes and Measures: Geometric mean titers (GMTs) of the anti-RBD; the ratio of GMTs for analysis of demographic, disease, and treatment variables; the percentage of neutralization of anti-RBD antibodies; and the correlation between anti-RBD and nAb responses to the COVID-19 vaccines. Results: This study enrolled 453 patients (mean [SD] age, 60.4 [13,1] years; 253 [56%] were female). Of 450 patients, 273 (61%) received the BNT162b2 vaccine (Pfizer), 160 (36%) received the mRNA-1273 vaccine (Moderna), and 17 (4%) received the JNJ-7846735 vaccine (Johnson & Johnson). The GMTs of the anti-RBD for all patients were 1.70 (95% CI, 1.04-2.85) before vaccination, 18.65 (95% CI, 10.19-34.11) after the first dose, 470.38 (95% CI, 322.07-686.99) at 1 month after the second dose, 425.80 (95% CI, 322.24-562.64) at 3 months after the second dose, 447.23 (95% CI, 258.53-773.66) at 6 months after the second dose, and 9224.85 (95% CI, 2423.92-35107.55) after the third dose. The rate of threshold neutralization (≥30%) was observed in 203 of 252 patients (80%) 1 month after the second dose and in 135 of 166 patients (81%) 3 months after the second dose. Anti-RBD and nAb were highly correlated (Spearman correlation coefficient, 0.93 [0.92-0.94]; P < .001). Three months after the second dose, anti-RBD titers were lower in male vs female patients (ratio of GMTs, 0.52 [95% CI, 0.34-0.81]), patients older than 65 years vs patients 50 years or younger (ratio of GMTs, 0.38 [95% CI, 0.25-0.57]), and patients with hematologic malignant tumors vs solid tumors (ratio of GMTs, 0.40 [95% CI, 0.20-0.81]). Conclusions and Relevance: In this cross-sectional study, after 2 doses of an mRNA vaccine, anti-RBD titers peaked at 1 month and remained stable over the next 6 months. Patients older than 65 years of age, male patients, and patients with a hematologic malignant tumor had low antibody titers. Compared with the primary vaccine course, a 20-fold increase in titers from a third dose suggests a brisk B-cell anamnestic response in patients with cancer.